Whenever premature birth interrupts normal retinal vascularization of the developing eye, retinopathy of prematurity (ROP) can occur. When ROP was first reported in the 1940?s, it was associated with high, oxygen delivery to preterm infants. Though oxygen delivery to preterm infants is now carefully regulated, ROP is still a common occurrence. In very low birthweight infants (birth weights <1500g), ROP incidence exceeds 25%. Despite treatment for advanced disease, ROP is a leading cause of visual disability in the U.S. and abroad. The current understanding of ROP is that ROP initiates due to a delay in retinal vascularization which leads to retinal ischemia and ultimately to advanced, vasoproliferative disease. Though photocoagulation and vitrectomy are used to treat late stage ROP, there is a high unmet need for preventative agents. An important mission of Zietchick Research Institute, LLC (ZRI), is to develop new therapeutics for maternal/child eye health. In this Phase I SBIR grant project, ZRI will establish proof-of-principle that a hormone-enriched therapeutic for premature infants can serve as a game-changing strategy for ROP prevention. In this proposal, ZRI will first present strong preliminary data that two related hormones, human chorionic gonadotropin (hCG) and luteinizing hormone (LH), influence retinal vessel formation. ZRI will next present two research aims. For Aim I, ZRI will quantify levels of hCG and LH on stored biosamples from human preterm infants to show that these hormone levels are significantly lower in ROP cases compared to controls. For Aim 2, ZRI will demonstrate that neonatal mice who lack hCG/LH receptors have abnormal retinal vascularization, resembling human ROP. Successful completion of these two aims will allow ZRI to proceed to Phase II to develop a hormone-based therapeutic for pre-clinical testing which will ultimately reduce the burden of pediatric blindness all over the world.